The invention relates to a process for obtaining alpha-campholenic aldehyde, which is useful as an aroma chemical and as a synthetic intermediate for other aroma chemicals, particularly those with a sandalwood odor, and also for some pharmaceuticals.
A practically sound method for obtaining xcex1-campholenic aldehyde was described by B. Arbuzow in 1935 (Berichte der Deutschen Chemischen Gesellschaft, 1935, B.II, S.1430-1435).
According to this article, xcex1-pinene oxide rearranged exothermically in the presence of zinc bromide catalyst in benzene solvent to give about 80% yield of alpha-campholenic aldehyde (Scheme 1). Since then, this batch process, or variations thereof, has been described in numerous publications and patents.
Most of these variations consisted in using different Lewis acids as catalysts, and also different solvents. For instance, zinc chloride in benzene gave a 70% yield of xcex1-campholenic aldehyde (R. I. Naipawer and W. M. Easter, U.S. Pat. No. 4,052,341, 1977; Chem. Abstr. 88: 22229a, 1978). Boron trifluoride etherate in toluene at minus 50xc2x0 C. gave 73% yield (M. Vialemaringe, et al. C. R. Acad. Sci. Paris, 1999, t. 2, Serie II c, pp. 449-454). A number of Lewis and Bronsted acids and solvents had been examined by J. Kaminska, et al. in: Recl. Trav. Chim. Pays-Bas, 1992, 111, pp. 432-437. Best results were obtained, again, with zinc bromide and zinc chloride. 
The rearrangement of xcex1-pinene oxide into xcex1-campholenic aldehyde is stereospecific. For example, (xe2x88x92)-xcex1-pinene oxide was converted to (+)-R-xcex1-campholenic aldehyde (Scheme 2, a) in 75% yield in the presence of zinc bromide in refluxing toluene (C. Chapuis and R. Brauchli, Helv. Chim. Acta, 1992, Vol. 75, pp. 1527-1546). Respectively, (+)-xcex1-pinene oxide gives (xe2x88x92)-S-xcex1-campholenic aldehyde (Scheme 2, b). 
From a practical standpoint, these batch methods for the rearrangement of xcex1-pinene oxide into xcex1-campholenic aldehyde have a series of drawbacks, namely low throughput per unit of equipment volume, and also low turnover numbers in moles of product per mole of catalyst. For instance, in all cited above references the turnover ranges from 20 to 200 moles/mole.
The total turnover can be improved by repeatedly recycling the catalyst as disclosed in WO 00/01793 (P. Davey, et al.). The rearrangement is carried out in toluene in the presence of zinc bromide. After the reaction, zinc bromide is extracted from the mixture with water. This aqueous solution is reused in the next batch reaction after azeotrope removal of the water. Although this procedure can increase the turnover, it is laborious and does not improve the throughput.
Certain heterogeneous catalysts have been employed for the rearrangement of xcex1-pinene oxide into xcex1-campholenic aldehyde. For example, it was reported that a selectivity of about 78% to xcex1-campholenic aldehyde has been achieved in a batch process on highly dealuminated specially pretreated H-US-Y zeolite at 0xc2x0 C. in toluene solvent. The reaction took 24 hours at catalyst loading 13.3% of the weight of xcex1-pinene oxide. See: W. F. Hxc3x6lderich, et al. Catalysis Today, 1997, Vol. 33, pp. 353-366.
Zeolite Ti-xcex2 has been reported to give a high selectivity towards xcex1-campholenic aldehyde in a gas-phase continuous process at 90xc2x0 C. However, the throughput in this process was significantly reduced because xcex1-pinene oxide has been fed in the reactor strongly diluted (to 1%) with carrier gas (nitrogen) and n-heptane or dichloroethane as a co-adsorbate in order to decrease the formation of by products. See: P. J. Kunkeler, et al. Catalysis Letters, 1998, Vol. 53, pp. 135-138.
Therefore, the need still exists for a continuous and yet commercially practical technique for the rearrangement of xcex1-pinene oxide into xcex1-campholenic aldehyde.
Among other aspects, the present invention is based on the surprising discovery that a continuous process for obtaining optically active or racemic xcex1-campholenic aldehyde by a catalytic rearrangement of optically active or racemic xcex1-pinene oxide can also be commerically practicable.
In one embodiment, the method comprises continuously feeding xcex1-pinene oxide to a mixture including catalyst(s) and solvent(s), where the solvent(s) have a boiling point higher than the boiling point of xcex1-campholenic aldehyde, under conditions sufficient to provide for the complete, or at least partial, conversion of xcex1-pinene oxide into xcex1-campholenic aldehyde. The process further includes continuously removing xcex1-campholenic aldehyde from the reaction zone by suitable techniques such as distillation.